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Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study

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Summary

Background

The declining efficacy of existing antibiotics potentially jeopardises outcomes in patients undergoing medical procedures. We investigated the potential consequences of increases in antibiotic resistance on the ten most common surgical procedures and immunosuppressing cancer chemotherapies that rely on antibiotic prophylaxis in the USA.

Methods

We searched the published scientific literature and identified meta-analyses and reviews of randomised controlled trials or quasi-randomised controlled trials (allocation done on the basis of a pseudo-random sequence—eg, odd/even hospital number or date of birth, alternation) to estimate the efficacy of antibiotic prophylaxis in preventing infections and infection-related deaths after surgical procedures and immunosuppressing cancer chemotherapy. We varied the identified effect sizes under different scenarios of reduction in the efficacy of antibiotic prophylaxis (10%, 30%, 70%, and 100% reductions) and estimated the additional number of infections and infection-related deaths per year in the USA for each scenario. We estimated the percentage of pathogens causing infections after these procedures that are resistant to standard prophylactic antibiotics in the USA.

Findings

We estimate that between 38·7% and 50·9% of pathogens causing surgical site infections and 26·8% of pathogens causing infections after chemotherapy are resistant to standard prophylactic antibiotics in the USA. A 30% reduction in the efficacy of antibiotic prophylaxis for these procedures would result in 120 000 additional surgical site infections and infections after chemotherapy per year in the USA (ranging from 40 000 for a 10% reduction in efficacy to 280 000 for a 70% reduction in efficacy), and 6300 infection-related deaths (range: 2100 for a 10% reduction in efficacy, to 15 000 for a 70% reduction). We estimated that every year, 13 120 infections (42%) after prostate biopsy are attributable to resistance to fluoroquinolones in the USA.

Interpretation

Increasing antibiotic resistance potentially threatens the safety and efficacy of surgical procedures and immunosuppressing chemotherapy. More data are needed to establish how antibiotic prophylaxis recommendations should be modified in the context of increasing rates of resistance.

Funding

DRIVE-AB Consortium.

Introduction

Antibiotics are integral to modern health care and have enabled the use of invasive surgical or immunosuppressive medical procedures that depend on the ability to keep the body free of infection.1 Prophylactic antibiotics are used routinely as part of surgery, organ transplantation, and cancer chemotherapy to prevent infections.2, 3 Increasing antibiotic resistance threatens the efficacy of these procedures and could result in adverse clinical outcomes, including increased rates of morbidity, amputation, or death.1

In 2011, in the USA, an estimated 157 500 surgical site infections were associated with inpatient surgery.4 Surgical site infections reportedly lead to a 3% mortality rate, and patients who develop such infections have a two to 11 times higher mortality rate than those who do not.5 According to the US Centers for Disease Control and Prevention (CDC), every year, about 650 000 patients with cancer receive chemotherapy in the USA, of whom about 10% acquire an infection that necessitates a hospital visit.6

We investigated the potential consequences of increases in antibiotic resistance on the ten most common surgical procedures and immunosuppressing cancer chemotherapies that rely on antibiotic prophylaxis in the USA. We identified meta-analyses of randomised controlled trials or quasi-randomised controlled trials (allocation done on the basis of a pseudorandom sequence—eg, odd/even hospital number or date of birth, alternation) that assessed the efficacy of antibiotic prophylaxis in preventing infections and infection-related deaths for these procedures. We then applied these effect sizes to estimate the number of additional infections and infection-related deaths in the USA for different scenarios of reduction in the efficacy of antibiotic prophylaxis as a consequence of increasing antibiotic resistance. Finally, we estimated the existing proportion of infections after surgery and cancer chemotherapy caused by organisms resistant to standard prophylactic antibiotics in the USA.

Research in context

Evidence before this study

Individual studies have previously investigated the effect of increasing antibiotic resistance on a reduction in the efficacy of antibiotic prophylaxis, but a global estimate of the effect of declining antibiotic efficacy is unknown. We did two main literature searches: one to identify studies published between January, 1950, and May, 2015, that investigate the efficacy of antibiotic prophylaxis on clinical outcomes of surgical procedures and cancer chemotherapy, and one to review the existing evidence on the effect of antibiotic resistance on clinical outcomes (including infection and mortality rates) for the same procedures (studies published between January, 1990, and May, 2015). No language restrictions were applied. Besides the different meta-analyses and reviews listed for each procedure in appendix pp 11–12, we identified two main reviews that studied the efficacy of antibiotic prophylaxis in preventing infections across different surgical procedures. By contrast, the published literature about the effects of antibiotic resistance on infection rates after various medical procedures was sparse. We were able to identify studies of the effects of changes in prophylactic regimens on infection rates for several procedures.

Added value of this study

To our knowledge, this study provides the first estimates of the potential effect of antibiotic resistance on the efficacy of antibiotic prophylaxis for a range of surgeries and cancer treatments. By using data from the published literature on both the effects of antibiotic prophylaxis on infection rates and on the effects of antibiotic resistance on infections rates for different procedures, we were able to provide estimates of the potential effect of antibiotic resistance on clinical outcomes after major medical procedures.

Implications of all the available evidence

Our study confirms findings that increasing antibiotic resistance potentially threatens the safety and efficacy of surgical procedures and immunosuppressing chemotherapy. These results provide a basis for further studies investigating the effects of antibiotic resistance on infection rates and other clinical outcomes across a wide range of medical procedures.

Section snippets

Search strategy and selection criteria

We did literature searches in PubMed, ScienceDirect, and the Cochrane Database of Systematic Reviews to identify meta-analyses of randomised controlled trials or quasi-randomised controlled trials that assessed the efficacy of antibiotic prophylaxis on outcomes of surgical procedures and immunosuppressing cancer chemotherapy. We searched the reference lists of relevant papers for additional, previously unidentified meta-analyses. We identified reports and clinical guidelines on antibiotic

Results

We identified 31 meta-analyses that met our inclusion criteria. Of these 31 meta-analyses for 31 procedures, we focused on the ten most commonly performed surgical procedures in the USA for which the benefits of antibiotic prophylaxis in reducing infection rates are well established and on immunosuppressing cancer chemotherapy (appendix pp 8–10).

We found two randomised controlled trials for abdominal hysterectomy and pacemaker implantation that were published after the meta-analyses. Because

Discussion

In addition to making the treatment of patients with infections difficult, antibiotic resistance also limits the efficacy of antibiotic prophylaxis, leading to worse outcomes in patients undergoing surgical procedures or receiving immunosuppressive cancer chemotherapy. The published literature supports the important role of antibiotics for these patients. A 30% reduction in the efficacy of antibiotic prophylaxis by comparison with effect sizes recorded in randomised controlled trials done

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